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ID PMID Title PublicationDate abstract
11161117 Victimization in chronic fatigue syndrome and fibromyalgia in tertiary care: a controlled 2001 Jan The authors studied the prevalence and characteristics of different forms of victimization in 95 patients suffering from chronic fatigue syndrome (CFS) or fibromyalgia (FM) compared with a chronic disease group, including rheumatoid arthritis (RA) and multiple sclerosis (MS) patients, and a matched healthy control group. The authors assessed prevalence rates, nature of victimization (emotional, physical, sexual), life period of occurrence, emotional impact, and relationship with the perpetrator by a self-report questionnaire on burdening experiences. CFS and FM patients showed significantly higher prevalences of emotional neglect and abuse and of physical abuse, with a considerable subgroup experiencing lifelong victimization. The family of origin and the partner were the most frequent perpetrators. With the exception of sexual abuse, victimization was more severely experienced by the CFS/FM group. No differences were found between healthy control subjects or RA/MS patients, and between CFS and FM patients. These findings support etiological hypotheses suggesting a pivotal role for chronic stress in CFS and FM and may have important therapeutic implications.
9767453 Amidolytic and peptidolytic activities of immunoglobulin G present in sera from patients w 1998 Sep Polyclonal immunoglobulin G (IgG) from healthy subjects was found to be capable of hydrolyzing carbobenzoxy-Val-Gly-Arg-p-nitroanilide (a synthetic chromogenic substrate for trypsin) and D-Pro-Phe-Arg-p-nitroanilide (a substrate for plasma kallikrein). Statistically significant elevation of activity against the former substrate was found in patients with rheumatoid arthritis (RA), but not in patients with Sjogren's syndrome (SjS) or systemic lupus erythematosus (SLE). On the other hand, IgG samples from the patients with these three autoimmune diseases showed reduced activity against d-Pro-Phe-Arg methylcoumarinamide, although the differences were not statistically significant. Preliminary studies have shown that two out of three IgG samples from RA patients exhibited the activity of cleaving a pentapeptide, Gln-Arg-Arg-Ala-Ala, whereas virtually no cleavage of the same peptide was observed with IgG from healthy controls or from patients with SjS or SLE.
11106928 Simultaneous peripubertal onset of multireactive autoimmune diseases with an unusual long- 2000 Nov Although it is well known that patients with type 1 diabetes mellitus are susceptible to other autoimmune diseases, the simultaneous occurrence of clustered distinct autoimmune diseases is uncommon. We report a 16-year-old girl, previously diagnosed as having coeliac disease and IgA deficiency, who at 13 years of age developed a clustering of distinct autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis (RA) and euthyroid autoimmune thyroiditis, eventually resulting in a simultaneous long-term remission. The clinical picture was associated with a functional immunodeficiency characterized by a defect in proliferative responses to T cell predominant mitogens and a normal response to the B cell predominant mitogen. In addition, the T cell activation markers HLA-DR, IL-2 receptor and transferrin receptor) were not upregulated. The clinical course of this immunodeficiency paralleled the outcome of the autoimmune diseases. After the abrupt onset, spontaneous clinical remission of both diabetes mellitus and RA was observed. Insulin was first reduced in dose and then discontinued completely at 15 months, in the presence of normal C peptide secretion and normal metabolic control (HbA1c 5.8%). Anti-glutamate decarboxylase (GAD65) and anti-IA-2 antibodies remained persistently high. During the remission phase a normalization of the functional immune defect was observed. The gradual resolution of the multisystemic diseases as well as the normalization of immune function in our patient is unusual. This case may be of considerable value in furthering our knowledge of the immunological mechanisms implicated in these rare multireactive syndromes.
9002043 Corticotropin releasing hormone promoter region polymorphisms in rheumatoid arthritis. 1997 Jan The regulation of the human corticotropin releasing hormone (CRH) gene is of interest since it mediates the interaction of stress events and inflammatory signals on the hypothalamo-pituitary-adrenal axis. Patients with rheumatoid arthritis (RA) have impaired CRH response to stress so that polymorphisms in the 5' regulatory region of the CRH gene could be responsible for decreased CRH responsiveness. To examine whether patients with RA have polymorphisms of the regulatory region of CRH, we amplified fragments of the 3.7 kb genomic DNA from 5 unrelated patients with RA and 2 controls. DNA sequencing revealed 3 nucleotide variants. These variants have been characterized as a T-->C base substitution located at position 1273 (alleles A1 and A2) and at position 2942 (alleles B1 and B2), and a C-->G base substitution located at position 95 (alleles C1 and C2), respectively, of the Genbank entry x67661. These substitutions lead to the destruction of the recognition site for AflIII (position 1273) and CviJI (position 95), and an introduction of a recognition site for BsmAI (position 2942) restriction enzymes, respectively. Three of 5 patients with RA were heterozygous for all 3 polymorphisms observed, while the 2 polymorphisms at positions 1273 and 2942 were represented in one control only. Post polymerase chain reaction (PCR) restriction fragment length polymorphism was performed to investigate the frequency of the polymorphisms in 99 healthy unrelated Caucasians and 28 members of CEPH (Centre d'Etudes du Polymorphisme Humaine) families. The AflIII, BsmAI, and CviJI polymorphisms cosegregate absolutely in both the controls and the CEPH families. The frequency for allele 1 was 0.869, while that for allele 2 was 0.131, with the following observed genotype frequencies: A1/A1 0.75; A1/A2 0.23; A2/A2 0.02. The T-->C base substitution at position 2942 leads to destruction of a consensus sequence for transcription factor GH-CSE2. These novel polymorphisms should therefore be considered in studies of CRH gene expression and may play a role in the pathogenesis of RA.
11752503 Increased endothelial expression of HLA-DQ and interleukin 1alpha in extra-articular rheum 2001 Dec OBJECTIVE: To investigate markers of endothelial activation in muscle biopsies from rheumatoid arthritis (RA) patients with and without extra-articular manifestations (ExRA). PATIENTS AND METHODS: Nine consecutive ExRA patients were compared with nine RA controls without ExRA, matched for age, sex and duration of RA. Muscle biopsies were obtained from the lateral vastus or anterior tibial muscle. Macrophage and lymphocyte CD markers, HLA molecules, cytokines and adhesion molecules were investigated using immunohistochemistry, and stainings were evaluated using computer image analysis and conventional microscopy. Serum concentrations of soluble adhesion molecules, tumour necrosis factor alpha (TNF-alpha) and rheumatoid factor (RF) were determined using immunoassays. RESULTS: The number of HLA-DQ-positive capillaries (P=0.039) and the expression of interleukin 1alpha (IL-1alpha) in endothelial cells (mean pairwise difference 0.26%; 95% confidence interval 0-0.52) were increased in ExRA patients compared with non-ExRA controls. There were no signs of inflammatory cell infiltrates or fibre degeneration. Serum levels of TNF-alpha, the soluble form of intercellular adhesion molecule 1, the soluble form of vascular cell adhesion molecule 1 and IgM RF were increased in the ExRA group. CONCLUSION: The increased expression of HLA-DQ and IL-1alpha may indicate systemic endothelial activation in extra-articular RA, which could be of importance for cardiovascular comorbidity and mortality in such patients.
10769429 [Osteoporosis in rheumatoid arthritis--significance of alfacalcidol in prevention and ther 2000 Besides localised osteopenia, patients with rheumatoid arthritis (RA) with or without corticosteroids develop in 30-50% osteoporosis induced by several factors and thus a higher risk of fractures. Bone loss appears very early and correlates directly with disease activity and also later with the negative effects of restrictive mobility. Corticosteroids reduce as a pathogenetic co-factor intestinal calcium absorption and increase renal calcium excretion resulting in compensatory increased PTH-release and increased sensitivity of bone to PTH. In addition, corticosteroids inhibit osteoblast function as well as the favourable effects of growth factors and sex hormones on bone. It has recently been recognised that the expression of D-hormone receptors (VDRs) is suppressed by these medications and that corticosteroids probably induce VDR disorders. The negative influence of corticosteroids on muscle strength (indirectly--via increased PTH-levels, lowered IGF-1-levels or reduced D-hormone activity) is a feature which has been underestimated. The demonstrated drop in 1,25(OH)2D3 (D-hormone) levels in patients with RA in correlation with C-reactive protein (CRP) is of significance in the pathogenesis of RA-induced osteoporosis and could further promote the process of inflammation. There is a general consensus that cytokines (e.g. IL-1, IL-6, IL-12, TNF-alpha) induce bone resorption in inflammatory rheumatic diseases. There are, however, new findings which show that cytokines like TNF-alpha also interfere with bone formation by promoting apoptosis of osteoblasts and reduce the muscle strength, too. D-hormone preparations (alfacalcidol, calcitriol) possess immunoregulatory effects in vitro and in vivo by inhibiting the cytokines IL-1, IL-6, TNF-alpha and particularly IL-12. At the cellular level, D-hormone reduces the expression of Th1 helper cells directly or indirectly by inhibition of IL-12 from monocytes. Therapy with alfacalcidol or calcitriol results in increased production of Th2 helper cells which produce bone protective cytokines like IL-4 and IL-10. It is important to know that D-hormone protects osteoblasts against TNF-alpha-induced cell death. After conversion to D-hormone in the liver and bone, alfacalcidol antagonises the above described pathogenetic factors of the corticosteroids. D-hormone is one of the body's own immunoregulators, which is produced in macrophages in cases of need to reduce immunological overreactions in a feed-back loop. Improved understanding of the pathogenesis of corticosteroid-induced osteoporosis and of the pharmacological effects of alfacalcidol in this type of iatrogenic bone loss as well as the results of specific animal models simulating bone loss in inflammatory diseases explain the favourable effects of alfacalcidol in this indication. Various clinical studies have demonstrated clearly that alfacalcidol retards corticosteroid-induced bone loss in contrast to plain vitamin D. Due to its immunomodulating properties, alfacalcidol is particularly suitable for RA-induced bone loss and for the prevention of transplantation osteoporosis, and an adjuvant contribution to the disease-modifying therapy of RA and to the immunosuppressive therapy after transplantation can not be excluded.
10460948 Chronic rheumatoid arthritis complicated by myeloperoxidase antineutrophil cytoplasmic ant 1999 We report a myeloperoxidase antineutrophil cytoplasmic antibody-positive rheumatoid arthritis patient who developed necrotizing crescentic glomerulonephritis. Steroid therapy was given combined with an immunosuppressant agent, and double-filtration plasmapheresis was started with the aim of removing antibodies from the blood. This therapeutic regimen was found to be useful.
10427809 Acute anterior forearm compartment syndrome following wrist arthrodesis. 1999 Jun The authors report a case of anterior compartment syndrome in the forearm following total wrist arthrodesis via a dorsal approach. As far as they know this is the second case reported.
9144352 Synovial fluids from patients with osteoarthritis and rheumatoid arthritis contain high le 1997 May High levels of immunoreactive and biologically active parathyroid hormone-related peptide (PTHrP) were detected in synovial fluids from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). The levels of PTHrP immunoreactivity in synovial fluids, measured by a two-site immunoradiometric assay (IRMA) which detects hPTHrP(1-72) or longer peptides and a radioimmunoassay (RIA) specific to the carboxy-terminal portion of hPTHrP, were 3.2 +/- 0.3 pmol of hPTHrP(1-86)/l and 61 +/- 7.0 pmol of hPTHrP(109-141)/l in OA patients (mean +/- SE, n = 23), and 4.8 +/- 0.8 pmol of hPTHrP(1-86)/l and 164 +/- 30 pmol of hPTHrP(109-141)/l in RA patients (n = 26). Synovial fluid PTHrP levels distributed above the normal plasma reference ranges in each assay (0.7-2.6 pmol of hPTHrP(1-86)/l; 16-60.6 pmol of hPTHrP(109-141)/l). After concentration using sequential cation-exchange and reverse-phase chromatography, synovial fluid exhibited the activity that stimulated cyclic adenosine monophosphate (cAMP) accumulation in osteoblastic ROS 17/2.8 cells expressing PTH/PTHrP receptors. The cAMP accumulation activity in synovial fluid was sensitive to coincubation with excess hPTHrP(3-40), a PTH/PTHrP receptor antagonist, and was completely neutralized by preincubation with a monoclonal antibody specific to hPTHrP but not PTH. Immunohistochemical analysis of RA synovium revealed that PTHrP was localized in fibroblast-like cells in the synovial pannus invading articular cartilage. Our data show that PTHrP is produced locally by the diseased synovial tissue and released into synovial fluid at high concentrations, allowing us to hypothesize that PTHrP plays a novel role as a paracrine/autocrine factor in the pathology of OA and RA.
11831013 [Cytopenia associated with low dose pulse methotrexate in the treatment of rheumatoid arth 2001 Dec OBJECTIVES: To assess the associated risk factors of methotrexate (MTX)-induced cytopenia in rheumatoid arthritis (RA). METHODS: We followed 420 patients started on MTX for RA. We evaluated the frequency and clinical significance of patients with cytopenia related to MTX therapy. RESULTS: The prevalence of patients remaining in the follow-up in the MTX treatment was 21% at 60 months. eighty-seven patients (21%) continued treatment. The treatment termination in MTX was 28% for toxicity, 78 (19%) for no effect, 70 (17%) for relapse and 116 (28%) for toxicity and 69 (16%) for other reasons. A total of 10 patients with cytopenia related to MTX therapy were identified among them. The prevalence of cytopenia, including leukopenia (n = 6), thrombocytopenia (n = 3) and pancytopenia (n = 1), estimated to be 2.4% in MTX treated RA patients. Patients with cytopenia received 2.5-8 mg/w over a mean duration of 60.0 months (10-119 months). nine of 10 patients received NSAIDs with MTX therapy. The presence of renal abnormality (Cr > 1.2 mg/d) was in 3 cases, age over 70 years old in 4 patients, body weight under 50 kg in 8 patients, mean corpuscular volume (MCV) over 100 fl in 2 patients. High MCV value (over 94 fl) was in 7 patients, 6 of whom had some symptoms including fever (n = 3) and oral mucosa/lip abnormalities (n = 3). Low MCV value (under 84 fl) was in 3 patients, who had no symptom but arthralgia and no renal abnormality. And they were younger and received MTX in shorter period than high MCV group. CONCLUSIONS: In patients with high MCV (over 94 fl), most hematological toxicities seen during the course of MTX therapy can be predictable. But, some patients may develop unpredictable hematological reaction. We need to monitor hematological examination frequently and observe patients closely for the appearance of hematological toxicity throughout the presctiption period of MTX irrespective of the duration of treatment.
11225250 [The correlation of cytokines TNF alpha, IFN-gamma, Epo with anemia in rheumatoid arthriti 2000 Nov OBJECTIVE: To elucidate the characteristics of anemia of chronic disease(ACD) in rheumatoid arthritis(RA), and the role of TNF alpha, IFN-gamma and Epo in the pathogenesis of ACD. METHOD: Serum TNF alpha and IFN-gamma levels in RA patients and serum Epo levels in RA with ACD were measured by ELISA. Serum iron status profile in RA patients were also detected. The effects of TNF alpha and IFN-gamma on cobalt-induced erythropoietin production in human hepatic cancer cells(HepG2) were examined. The effect of TNF alpha and IFN-gamma erythroid colony formation (CFU-E and BFU-E) of normal bone marrow cells, and the effect of serum from RA patients and Epo on CFU-E yields of RA bone marrow cells. RESULT: Serum TNF alpha or IFN-gamma in RA and RA with ACD patients were higher than those in normal controls, and were inversely correlated with hemoglobin, and serum iron levels. Serum Epo levels in ACD patients were lower than those in iron-deficiency anemia patients with comparable hemoglobin level. TNF alpha and IFN-gamma could specifically inhibit cobalt-induced Epo production in HepG2 cells, and suppressed normal bone marrow BFU-E and CFU-E growth in a dose-dependent manner. Bone marrow CFU-E yields of RA patients were also suppressed by their own serum. The inhibitory effects of TNF alpha, IFN-gamma or serum from RA patients on erythroid colony formation could be corrected by the addition of rhEpo. CONCLUSION: It suggested that there were hematopoietic inhibiting factors in the serum of RA patients. TNF alpha or IFN-gamma was involved in the pathogenesis of anemia in RA patients. Administration of rhEpo might be beneficial for anemia of RA patients.
10632674 Osteoblasts and stromal cells isolated from femora in rheumatoid arthritis (RA) and osteoa 2000 Feb We investigated both in vitro and ex vivo the role of mature osteoblasts (OB) and bone marrow stromal cells (BMSC) in RA and OA by analysing the expression of the following IL-6-type cytokines: IL-11, leukaemia inhibitory factor (LIF), oncostatin M (OSM) and IL-6. OB and BMSC were isolated from femora of RA, OA and post-traumatic (PT) patients, cultured in vitro in the presence or absence of IL-1beta and tumour necrosis factor-alpha (TNF-alpha), and assessed for the production and mRNA expression of IL-6-type cytokines. Trabecular bone biopsies were obtained from the inner portions of femoral heads and used for cytokine in situ immunostaining. Cultured OB and BMSC from different patients constitutively secreted IL-11 and IL-6 but not OSM. LIF was secreted only by BMSC, at very low levels. Interestingly, IL-11 basal production was significantly higher in BMSC than in OB in all three groups tested. IL-1beta and TNF-alpha strongly stimulated IL-6-type cytokine release (except for OSM) by both OB and BMSC. OSM was expressed only at mRNA levels in all groups studied. Cytokine immunostaining on bone biopsies confirmed the data obtained on cultured cells: IL-11, IL-6 and LIF proteins were detected both in mesenchymal (BMSC and OB) and mononuclear cells; OSM was found only in mononuclear cells. These data demonstrate that IL-6-type cytokines are constitutively expressed in the bone compartment in RA, OA and PT patients and can be secreted by bone cells at different stages of differentiation (BMSC and OB). This suggests that these cytokines may be involved in the mechanisms of bone remodelling in OA and RA.
9649224 VH usage and somatic hypermutation in peripheral blood B cells of patients with rheumatoid 1998 Jun The human antibody repertoire has been demonstrated to have a marked V-gene-dependent bias that is conserved between individuals. In RA patients, certain heavy chain V genes (VH) have been found to be preferentially used for encoding autoantibodies. To determine if such preferential use of VH genes in autoantibodies is associated with a general distortion of the V gene repertoire in RA patients, the VH composition of peripheral blood B cells was analysed among four RA patients and four age- and sex-matched healthy controls. Usage of individual VH genes (eight VH3 and three VH4 genes tested by hybridization with a set of gene-specific oligonucleotide probes) was highly biased among RA patients, but no evidence of a distortion in the bias was observed compared with healthy controls. However, the occurrence of somatic mutations in these VH genes (estimated by differential hybridization with motif-specific oligonucleotide probes targeted to CDR and FR of the tested genes, and by DNA sequence analysis) was strikingly different between patients and healthy subjects. The number of VH3 rearrangements that had accumulated somatic mutations and the number of mutations per rearrangement were significantly elevated in three of the four RA patients. A slight but not significant elevation in mutations among rearranged VH4 genes was also observed in these patients. These data suggest that although usage of individual VH genes among peripheral blood B cells is not affected by the disease, the autoimmune process may involve a significant fraction of the B cell compartment.
9384395 Vertical translocation: the enigma of the disappearing atlantodens interval in patients wi 1997 Dec This statistical comparison between patients with cervical myelopathy secondary to horizontal atlantoaxial subluxation and those with vertical translocation is designed to elucidate the mechanisms responsible for cranial settling and the effect of translocation on the development of spinal cord compression. In a 10-year study of a cohort of 256 patients, 186 suffered from myelopathy and 116 (62%) of these exhibited vertical translocation according to the Redlund-Johnell criteria. Vertical translocation occurred after a significantly longer period of disease than atlantoaxial subluxation (p < 0.001). Translocation was characterized clinically by a high cervical myelopathy with features of a cruciate paralysis present in 35% of individuals compared with 26% who exhibited horizontal atlantoaxial subluxation (p = 0.29), but there was a surprising paucity of cranial nerve problems. The patients with vertical translocation had a greater degree of neurological disability (p = 0.002) and poorer survival rates (p = 0.04). Radiologically, vertical translocation was secondary to lateral mass collapse and associated with a progressive decrease in the atlantodens interval ([ADI], r = 0.4; p < 0.001) and pannus (p = 0.003). Thirty percent of patients exhibited an ADI of less than 5 mm. This phenomenon has been termed pseudostabilization. The authors' studies emphasize that the ADI (frequently featured in the literature) is totally unreliable as an indicator of neuraxial compromise in the presence of vertical translocation.
9377843 [Somatostatin in peri-arthropathies of the shoulder: clinical effectiveness and tolerabili 1997 Mar In the last few years, the intra-articular administration of somatostatin, has been used in some diseases regarding rheumatology such as rheumatoid arthritis psoriatic arthritis and osteoarthritis, giving encouraging results. The objective of this study was to asses the efficacy and tolerability of subacromial-injection of somatostatin in 20 patients with painful shoulder. The study consisted of 3 injection administered every 4 days. The results revealed a significant improvement of the pain during active movement as well as joint excursion, and interference with daily activity immediately after the first injection. The good tolerability of the drug and the absence of unwanted side-effects allow us to foresee that the local-administration of somatostatin could be used in painful shoulder notably in those patients in which other drugs are not appropriate.
11868082 MRI of the arthritic finger joints: synovial membrane volume determination, a manual vs a 2002 Jan The aim of this study was to compare the stereology method for estimation of synovial volume on MR images with manually outlining method in inflammatory joint diseases. As manual outlining of the synovial volume is too time-consuming a method for clinical use, a less time-consuming methods are needed. Post-contrast 3D T1-weighted turbo gradient MR images of the finger (metacarpophalangeal and interphalangeal) joints (14 joints) were acquired from 11 patients with rheumatoid arthritis ( n=8) and reactive arthritis ( n=3). Manually outlined volume was taken as a gold standard and compared with stereologic volume estimation on transverse 1-mm-thick slices. The mathematical basis of the stereologic volume estimator is based on a two-step procedure: a 2D nucleator is used for estimation of the area of the synovial membrane on an MR slice and unbiased estimates of volumes are obtained by Cavalieri's principle. The 2D nucleator estimates the area of any object irrespective of its size, shape, and orientation by measuring the distance between a "central point" in the object and the intersections between the object boundary and radiating test lines. The total volume of 154 finger joints was estimated. A significant correlation between manual and stereologic estimations of synovial volumes was found (Spearman rho=0.71, P=0.002). Ninety-five percent limits of agreement were +/- 5-6 ml (14 finger joints per patient). The time used for volume determination in a patient varied from 1 to 2.5 h by manual outlining and from 0.5 to 1 h by stereologic determination. Stereologic volume estimation can provide measures of synovial volumes comparable to the manual outlining method and is less time-consuming. Stereologic volume estimation seems to be a clinically useful method, especially if it is integrated in the MR unit's workstation.
10589364 Combination DMARD treatment with parenteral gold and methotrexate. 1999 Nov INTRODUCTION: Both methotrexate (MTX) and gold sodium thiomalate (GSTM) have been shown to be very effective in the treatment of rheumatoid arthritis (RA) and to slow x-ray progression. The combination of both drugs could be useful because of their different and complimentary mechanisms of action. However, there is only one long-term study comparing this combination with MTX monotherapy. METHODS: In this prospective long-term observational study, all patients who started MTX treatment from 1980 to 1987 in one center were followed for 12-108 (mean 34.1) months. Ninety-seven patients were treated with MTX, while 126 patients received the combination MTX/GSTM, both drugs being given at the full dose. All patients had active disease, most of them long-lasting destructive RA not responsive to previous disease-modifying antirheumatic drug (DMARD) treatment. RESULTS: There were no significant differences in the demographic and baseline data between the two groups, with the exception of higher swollen joint counts (SJC) and C-reactive protein (CRP) in the combination group. In both groups the parameters of disease activity (erythrocyte sedimentation rate [ESR], CRP, SJC) improved significantly. A > 50% improvement in the SJC after 1 and 3 years was seen in 62% and 70% of patients in the MTX group, and in 55% and 85% of the patients in the combination group, respectively. A > 50% improvement in the ESR occurred in 54%/63% (MTX group) and in 49%/68% (combination group) for the same timepoints. There was no difference between the groups regarding the nature, frequency, or severity of side effects. A total of 20.6% (MTX) and 15.1% (combination) of patients were withdrawn for side effects. After 5 years, 54% of the patients in both groups were still being treated. CONCLUSION: This long-term observational study shows that the combination MTX/GSTM is well tolerated and is at least as effective as MTX single treatment. Taking into account the higher disease activity at baseline and the greater x-ray progression before baseline among the patients in the combination group, one may conclude that combination treatment is superior to monotherapy.
10893659 Treating osteoarthritis in practice--the TOP Study. 2000 This study consisted of two nationwide surveys. The first involved 209 general practitioners (GPs) from 22 sampling points in England, Scotland and Wales, and the second involved 510 patients with osteoarthritis (OA) (aged 60 years and above), rheumatoid arthritis (RA) or unspecified arthritis, who had visited their GP for treatment. The results showed that OA has a significant negative impact on patients' quality of life; 79% of patients stated that their condition limited their quality of life. Only 15% of GPs reported prescribing a conventional non-steroidal anti-inflammatory drug (NSAID) as first-line treatment for patients with arthritis. More than half (57%) stated that they would prescribe a simple analgesic or a compound analgesic before trying an NSAID. Forty four per cent of GPs stated that their main therapeutic objective when prescribing an NSAID was to minimise GI side-effects, and therefore start at a low dose. This implies that many patients are likely to be receiving sub-optimal doses. Experiencing breakthrough pain and GI side-effects were common reasons cited for patients re-presenting to GPs. GPs reported their expectation to prescribe GI protectants to a fifth (21%) of their patients on NSAIDs and estimated one in six patients (17%) take OTC products to relieve GI symptoms. This research demonstrates that there is considerable dissatisfaction with currently used treatment regimens for osteoarthritis, from both the GP and patient perspectives.
9404229 Mast cell activation in arthritis: detection of alpha- and beta-tryptase, histamine and eo 1997 Oct 1. Although mast cell hyperplasia is a feature of rheumatoid arthritis and osteoarthritis, the extent and nature of mast cell activation in joint disease have not been clearly established. 2. We have investigated the levels of mast cell tryptase and histamine and also of eosinophil cationic protein in synovial fluid collected from 31 patients with rheumatoid arthritis, 14 with seronegative spondyloarthritis and nine with osteoarthritis. Two RIAs for tryptase were employed: one with monoclonal antibody AA5, which was found to bind equally well to both alpha and beta isoforms on Western blots of the recombinant enzyme, and the other with antibody G5, which recognizes predominantly beta-tryptase. 3. alpha-Tryptase, which is likely to be released constitutively from mast cells, appeared to be the major form in synovial fluid, as the assay with antibody AA5 detected appreciably more tryptase than that with antibody G5. beta-Tryptase, which is released on anaphylactic activation of mast cells, was detected in 14 out of 45 synovial fluid samples studied, with concentrations of up to 12 micrograms/l measured by the G5 assay. The apparent levels of beta-tryptase, but not of alpha-tryptase, were closely correlated with those of histamine in the synovial fluid. Patients with osteoarthritis appeared to have a greater proportion of beta-tryptase in the synovial fluid than those with rheumatoid arthritis, as well as higher concentrations of histamine. Eosinophil cationic protein was present at high levels in the synovial fluid, although eosinophil numbers were low, and its concentrations were not correlated with the concentrations of the mast cell products. 4. These data suggest that anaphylactic degranulation of mast cells may have occurred to a greater extent in osteoarthritis than in rheumatoid arthritis, despite the relative lack of synovial inflammation in osteoarthritis. Although the eosinophil cationic protein detected may not reflect eosinophilic inflammation in the joint, the presence in synovial fluid of tryptase of both major forms, and of histamine, appears to indicate that mast cell products are secreted constitutively, as well as by processes of anaphylactic degranulation in rheumatoid arthritis, seronegative spondyloarthritis and osteoarthritis.
11345587 Distribution of HERV-LTR elements in the 5'-flanking region of HLA-DQB1 and association wi 2001 Mar We established the detailed polymorphism of the 5'-flanking region and the first exon of the human leukocyte antigen (HLA)-DQB1 alleles. One hundred and forty-five Spanish rheumatoid arthritis (RA) patients and 200 healthy voluntary blood donors from southern Spain along with 42 B-cell lines were analyzed for the presence of the retrovirus-derived long terminal repeats (LTRs) LTR3, LTR5, and LTR13. LTR3 positivity was always associated with certain DQB1 alleles, i.e., *0302, *0402, *0601, *0202, and *0305. Sequencing analysis of the 5'-flanking region of DQB1*0301, *0303 and *0502 alleles in homozygous B-cell lines showed the absence of LTR3 and a massive deletion of 5635 base pairs. The undetected deletion in the flanking region of some DQB1 alleles and a lack of stratification for HLA typing explain previously reported associations of the LTR3 element with RA and type I diabetes (IDDM). LTR5 showed identical distribution to LTR3, consistent with a previously suggested LTR3-LTR5 tandem arrangement. LTR13 positivity was associated with DQB1*0302, *0303, and *0402 alleles. Distributions of the LTR elements in all B-cell lines, RA patients, and controls could be explained entirely by linkage disequilibrium with DQB1 alleles, independently of the haplotypes carrying them. LTR elements are known to regulate gene expression. Therefore, a possible involvement of LTR13 in the association of DQB1*0302, *0303, and *0402 with IDDM requires further investigation. The sequencing results of the DQB1 first exon demonstrated that DQB1*0601 was generated by a recombination event between a DR53 and a non-DR53 haplotype. Our results shed new light on the phylogeny of the HLA region and the possible contribution of DQB1 to susceptibility to autoimmunity.